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Δευτέρα, 17 Απριλίου 2017

Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia


Ketamine may prove to be a potential candidate in treating the widespread drug addiction/substance abuse epidemic among patients with schizophrenia. Clinical studies have shown ketamine to reduce cocaine and heroin cravings. However, the use of ketamine remains controversial as it may exacerbate the symptoms of schizophrenia. Therefore, the aim of this study is to characterize the effects of ketamine on drug addiction in schizophrenia using the methylazoxymethanol (MAM) acetate rat model on operant IV methamphetamine (METH) self-administration. MAM was administered intraperitoneally (22 mg/kg) on gestational day 17. Locomotor activity test and later IV self-administration (IVSA) were then performed in the male offspring followed by a period of forced abstinence and relapse of METH taking. After reaching stable intakes in the relapse phase, ketamine (5 mg/kg) was administered intraperitoneally 30 min prior to the self-administration session. As documented previously, the MAM rats showed a lack of habituation in the locomotor activity test but developed stable maintenance of METH self-administration with no difference in operant behaviour to control animals. Results show that ketamine treatment significantly reduced the METH intake in the control animals but not in MAM animals. Ketamine effect on METH self-administration may be explained by increased glutamatergic signalling in the prefrontal cortex caused by the N-methyl-D-aspartate antagonism and disinhibition of GABA interneurons which was shown to be impaired in the MAM rats. This mechanism may at least partly explain the clinically proven anti-craving potential of ketamine and allow development of more specific anti-craving medications with fewer risks.


Postnatal LPS Challenge Impacts Escape Learning and Expression of Plasticity Factors Mmp9 and Timp1 in Rats: Effects of Repeated Training


Bacterial intoxication associated with inflammatory conditions during development can impair brain functions, in particular evolutionarily novel forms of memory, such as explicit learning. Little is known about the dangers of early-life inflammation on more basic forms of learning, for example, the acquisition of motor escape abilities, which are generally better preserved under pathological conditions. To address this limitation in knowledge, an inflammatory response was elicited in Wistar pups by lipopolysaccharide (LPS) injections (25 μg/kg) on postnatal days P15, P18 and P21. The acquisition of escape behaviour was tested from P77 by active avoidance footshock model and water maze. Open-field behaviour and blood corticosterone levels were also measured. Rat brain tissue was collected from pups 2 h post-injection and from adult rats which either underwent escape training on P77–P81 or remained untrained. mRNA levels of developmental brain plasticity factors MMP-9 and TIMP-1 were investigated in the medial prefrontal cortex and ventral/dorsal hippocampus. LPS-challenged rats displayed moderately deficient escape responses in both memory tests, increased freezing behaviour and, surprisingly, reduced blood cortisol levels. Mmp9 and Timp1, and their ratio to one another, were differentially altered in pups versus adult untrained rats but remained unchanged overall in rats trained in either learning task. Together, our data indicate that systemic pro-inflammatory response during early postnatal development has long-lasting effects, including on the acquisition of motor escape abilities and plasticity factor expression, into adulthood. Our data suggest that altered stress response could possibly mediate these deviations and repeated training might generate positive effects on plasticity under the employed conditions.


A sustaining rod increases necrosis of loop ileostomies: a randomized controlled trial



Defunctioning loop ileostomies (LI) are commonly used in colorectal surgery to reduce the potentially detrimental consequences of anastomotic leakages. However, stoma-related morbidity is high with up to 75% of patients having local complications. The aim of this study was to investigate the effect of a sustaining rod on the local complication rate.


In this prospective, multi-center, randomized controlled trial, subjects were allocated to either a rod or a rod-less protocol (NCT00959738). The primary outcome was local morbidity as measured by a stoma specific morbidity score (SSMS) during the first 3 months postoperatively.


Between August 2008 and July 2014, a total of 122 patients were enrolled in the study, of which 78 (63.8%) completed the study [44 (56.4%) rod, 34 (43.6%) rod-less]. There was no significant difference in the SSMS between the two groups. The incidence of necrosis or partial necrosis, however, was significantly increased in the rod group: 13 (29.5%) vs. 1 (2.9%) in the rod-less group (p < 0.01). The retraction rate did not differ significantly between the groups: two (4.5%) in the rod vs. five (14.7%) in the rod-less group (p = 0.13). High body mass index (BMI > 26) was associated with an odds ratio of 5 (p < 0.01) for severe stoma complications.


A rod-less technique for loop ileostomies reduces the risk of stomal necrosis, with a high BMI being an independent risk factor for stomal complications.


Surgical surprise in a case of loculated empyema


Cases of massive benign pleural effusion, presenting later as chronic empyema are a known entity. Surgical intervention in the form of tube thoracostomy, thoracotomy/video-assisted thoracoscopic evacuation of pus and decortication are needed as a routine. But sometimes a surgical surprise on the table, gives the tell-tale evidence of a missed aetiology for pleural effusion. We present here a rare case of chronic empyema left hemi thorax which turned out to be ruptured dermoid cyst of anterior mediastinum with massive pleural effusion which got infected on repeated thoracocentesis. A 23-year-old female, computer engineer presented with dyspnoea and dry cough of 3 months duration, associated with loss of appetite and weight. No history of fever. On examination, thin built, mild clubbing, tracheal shift to right with dullness/absent breath sounds on entire left chest. On investigation, image studies revealed massive left pleural effusion, repeated thoracocentesis done, recurrent effusion turned into pyothorax, tube thoracostomy done and empirical anti-tuberculous therapy started by chest physician. Finally, came for decortication, thoracotomy on table revealed evidence of ruptured dermoid cyst confirmed by histopathology. Patient recovered well and 6 months follow-up revealed no recurrence. Investigations did not give any clue for preoperative diagnosis in our case. Aetiology for chronic empyema is multifactorial. Ruptured anterior mediastinal benign cystic teratoma revealed on thoracotomy for empyema is a rare entity and only three cases are reported so far. We report another such rare case from south India.


RhoGDIα is a potential prognostic biomarker and controls telomere regulation in colorectal cancer


RhoGDIα is an essential regulator for Rho GTPases. Although RhoGDIα may serve as an oncogene in colorectal cancer (CRC), the underlying mechanism is still unclear. Here,we investigate the function, mechanism, and clinical significance of RhoGDIα in CRC progression. We founded that downregulation of RhoGDIα repressed CRC cell proliferation, motility and invasion. Overexpression of RhoGDIα increased DNA damage response signals at telomeres, and led to telomere shortening in CRC cells, also being validated in 26 pairs of CRC tissues. Mechanistic studies revealed that RhoGDIα can promote TRF1 expression through PI3K-Akt signal pathway. Moreover, RhoGDIα protein levels were strongly correlated with TRF1 in CRC tissues. A cohort of 297 CRC samples validated the positive relationship between RhoGDIα and TRF1, and revealed that RhoGDIα and TRF1 levels were negatively associated with CRC patients’ survival. Taken together, our results suggest that RhoGDIα regulate TRF1 and telomere length and may be novel prognostic biomarkers in colorectal cancer.

This article is protected by copyright. All rights reserved.

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Nasal ala reconstruction: Tunnelled island pedicle melolabial flap; jigsaw puzzle advancement flap; spiral flap; dog-ear island pedicle flap and banner melolabial transposition flap.


Skin tumours of the nasal ala are common and surgery is the treatment
of choice. Nasal ala reconstruction is challenging due to the reduced
mobility and unique features of its thick and sebaceous skin. The
natural arc of the ala and its boundary with the cheek are difficult
features to reproduce. One should bear in mind the functional and
cosmetic risks of nasal ala reconstruction. A distorted nasal contour
may impair the nasal valve; the alar rim may notch or elevate; facial
symmetry may be disrupted by blunting of the alar crease, trapdooring,
bridging of the nasofacial sulcus and poor colour and texture match.

Our aim is to review and compare the functional and cosmetic results
of different local flaps used to correct intermediate-thickness
defects on the nasal ala after surgical excision of cutaneous tumours.
We present representative patients who were treated at our
Dermatological Surgery Unit from June 2015 to September 2016.

The choice of the flap was adapted to the patients' physiognomy and
the defects' size: tunnelled island pedicle melolabial flap [Figure
1]; jigsaw puzzle advancement flap [Figure 2]; spiral flap [Figure 3];
dog-ear island pedicle flap [Figure 4] and banner melolabial
transposition flap [Figure 5]. Surgery was performed under
loco-regional anaesthesia, in an outpatient basis, followed by
prophylactic antibiotic therapy. There were neither immediate
complications nor subsequent flap necrosis. The tumours were
completely excised.
Figure 1: Female, 86-year-old, nodular ulcerated basal cell carcinoma
in the nasal ala: tunnelled island pedicle melolabial flap. (a)
Surgical plan, (b) primary defect, (c) secondary defect after
tunnelling of the flap, (d) immediate post-operative, (e and f) result
after healing (10 months after surgery).

Click here to view
Figure 2: Male, 76-year-old, nodular basal cell carcinoma on the nasal
ala: jigsaw puzzle advancement flap. (a) surgical plan, (b) primary
and secondary defects, (c) anchoring sutures secure the flap in place;
(d) immediate post-operative, (e) result after healing (3 months after

Click here to view
Figure 3: Female, 76-year-old, nodular basal cell carcinoma on the
nasal ala: spiral flap, a combination of advancement and rotation. (a)
Surgical plan, (b) immediate post-operative, (c) result after healing
(2 months after surgery).

Click here to view
Figure 4: Female, 76-year-old, basal cell carcinoma on the nasal ala:
dog-ear island flap, combining two flaps: cheek advancement and
rotated island pedicle. (a) Surgical plan, (b) primary defect, (c)
immediate post-operative, (d) day 7 post-operative, (e) result after
healing (1 month after surgery).

Click here to view
Figure 5: Male, 83-year-old, two nodular basal cell carcinomas on the
nasal ala and dorsum: Banner's melolabial transposition flap. (a)
Surgical plan, (b) primary defect, (c) immediate post-operative, (d)
result after healing (7 months after surgery)

Click here to view

Facial symmetry was well preserved by the spiral and jigsaw puzzle
flaps [Figure 2] and [Figure 3]. The nasal sulcus was left intact by
the spiral flap as well as the tunnelled melolabial island flap
[Figure 1] and [Figure 3]. The melolabial flaps and the dog-ear island
flap allowed for the correction of larger defects on the nasal ala
[Figure 1], [Figure 4] and [Figure 5]. The dog-ear island flap [Figure
4] obtained a good result despite the large size of the primary
defect. Banner's melolabial transposition flap [Figure 5] was used to
correct a complex defect involving not only the nasal ala but also the
nasal dorsum and resulted in facial asymmetry due to trapdooring.

The small size of the defects that can be addressed by the spiral and
puzzle flaps may explain their superior cosmetic results.[1],[2] The
tunnelled melolabial island flap, although technically demanding, may
produce excellent results; compared to the cheek-to-nose interpolation
flap, the tunnelling technique offers the advantage of being one-stage
procedure. The dog-ear island flap is an adaptation of the cheek
advancement flap; despite its apparent complexity, it offers a viable
alternative to the melolabial flaps,[3] with a lower risk of trapdoor
effect and with proper preservation of the alar contour. The discussed
flaps are useful alternatives to the bilobed transposition flap and
the skin graft for the surgical reconstruction of the nasal ala.

When planning the surgery, it is important to assess the primary
defect on the nasal ala: size and location (medial or lateral), depth,
involvement of other cosmetic units/subunits and extension to the alar
rim, nasal tip or adjacent cheek. Several techniques have been
developed that are useful for the reconstruction of defects of the
nasal ala. Based on our experience and a review of the literature, we
present an algorithm [Table 1] to optimise the choices in the
reconstruction of intermediate-thickness defects in nasal ala. In
[Table 2], we review the main advantages and caveats of some of the
most useful surgical techniques for nasal ala
Table 1: Nasal ala reconstruction: What is the optimal approach
according to the defects' size and location?

Click here to view
Table 2: Nasal ala reconstruction: major advantages and potential
caveats of different surgical techniques

Click here to view

In the nasal ala, given the paucity of surrounding skin and the
importance of minimising nasal ala distortion, flaps that recruit skin
from a distant site should be considered. Mastering different
techniques is essential for a surgeon to optimise treatment for each
patient. At the end of the day, the best choice depends on many
factors and should be adapted on a case-by-case basis and to the
surgeon's expertise.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos

IJMS, Vol. 18, Pages 847: Overexpression of S-Adenosyl-l-Methionine Synthetase 2 from Sugar Beet M14 Increased Arabidopsis Tolerance to Salt and Oxidative Stress

The sugar beet monosomic addition line M14 is a unique germplasm that contains genetic materials from Beta vulgaris L. and Beta corolliflora Zoss, and shows tolerance to salt stress. Our study focuses on exploring the molecular mechanism of the salt tolerance of the sugar beet M14. In order to identify differentially expressed genes in M14 under salt stress, a subtractive cDNA library was generated by suppression subtractive hybridization (SSH). A total of 36 unique sequences were identified in the library and their putative functions were analyzed. One of the genes, S-adenosylmethionine synthetase (SAMS), is the key enzyme involved in the biosynthesis of S-adenosylmethionine (SAM), a precursor of polyamines. To determine the potential role of SAMS in salt tolerance, we isolated BvM14-SAMS2 from the salt-tolerant sugar beet M14. The expression of BvM14-SAMS2 in leaves and roots was greatly induced by salt stress. Overexpression of BvM14-SAMS2 in Arabidopsis resulted in enhanced salt and H2O2 tolerance. Furthermore, we obtained a knock-down T-DNA insertion mutant of AtSAMS3, which shares the highest homology with BvM14-SAMS2. Interestingly, the mutant atsam3 showed sensitivity to salt and H2O2 stress. We also found that the antioxidant system and polyamine metabolism play an important role in salt and H2O2 tolerance in the BvM14-SAMS2-overexpressed plants. To our knowledge, the function of the sugar beet SAMS has not been reported before. Our results have provided new insights into SAMS functions in sugar beet.

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Paediatric traumatic pneumomediastinum: the spinnaker sail sign


A 20-month-old female infant was admitted to the emergency room after being run over by a car. She presented with pallor and signs of impaired peripheral perfusion, despite being conscious and alert. Signs of respiratory distress were recognised. There was a bilateral decrease of respiratory murmurs at pulmonary auscultation and her heart sounds were also diminished. Her peripheral oxygen saturation was 94% and her respiratory rate was 54 breaths per minute. A cervical and thoracic crepitus were present. There were no alterations at abdominal examination. Her blood pressure was 142/58 mmHg.

She presented with a Glasgow Coma Scale score of 15 and had normal reactive pupils. Facial oedema was observed and an epicranial haematoma was also detected. Haematological workup revealed a haemoglobin value of 12.9 g/dL.

A supine chest radiograph showed left hydropneumothorax, right pneumothorax and pulmonary contusion. This exam also showed significant pneumomediastinum revealing the spinnaker sail sign,...

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Application of the isoniazid assay in dried blood spots using the ultra-performance liquid chromatography-tandem mass spectrometry

Publication date: Available online 18 April 2017
Source:Clinical Biochemistry
Author(s): Kyunghoon Lee, Sun-Hee Jun, Moon-Suk Choi, Sang Hoon Song, Jong Sun Park, Jae Ho Lee, Kyoung Un Park, Junghan Song
ObjectivesTherapeutic drug monitoring (TDM) of anti-tuberculosis (TB) drugs is important for proper treatment of TB. Dried blood spots (DBSs) are widely used for TDM because of their several advantages. Rifampicin and pyrazinamide assays with DBSs have already been developed. However, isoniazid (INH) assay for capillary DBSs have not been reported because of INH instability. We developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for measuring INH concentrations in venous and capillary DBSs.MethodsEach DBS was analyzed on an UPLC system. INH and internal standard (IS) concentrations were determined by multiple-reaction monitoring in positive ion mode. Analytical performances, including precision, linearity, and comparison of different types of specimens were determined. Further, the stability of INH in venous DBSs was tested.ResultsINH and IS were clearly separated in the UPLC-MS/MS system without matrix effect. Within-run precision and between-day precision were 2.68–8.02% and 2.54–5.45%, respectively. INH concentrations in venous DBS showed proportional bias compared with those in plasma (Slope: 0.8704) with good correlation. INH concentration in capillary DBS was slightly but not significantly higher than that in venous DBS.ConclusionsThe findings of our study show that the analytical performance of this novel method for capillary and venous DBSs was clinically acceptable for the TDM of INH.

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Eosinophilic meningitis

Eosinophilic meningitis: Meningitis with a high percentage of eosinophils (a type of white blood cell) in the cerebrospinal fluid (CSF). The usual cause is the parasite Angiostrongylus cantonensis, also known as the rat lungworm.

People become infected with this parasite by ingesting its larvae in raw or insufficiently cooked snails, slugs, freshwater prawns, frogs, or fish. Infection may also occur by consumption of fresh produce such as contaminated lettuce. When the larvae are ingested, they penetrate the intestinal tract, go into blood vessels, and eventually reach the meninges (the covering of the brain and spinal cord). The larvae usually die there shortly thereafter. An eosinophilic reaction develops in response to the dying larvae. It is manifested by an outpouring of eosinophils in the CSF.

Most cases of eosinophilic meningitis due to A. cantonensis have been reported in SE Asia and the Pacific Basin. However, in 2002 an outbreak of eosinophilic meningitis was reported in the US. The outbreak struck 12 young adults after they had returned from a trip to Jamaica. Symptoms included headache, neck pain, visual disturbances, and hyperesthesias. Nine of the travelers required hospitalization. A case-control study showed that consumption of a Caesar salad at one dinner was strongly associated with the development of the eosinophilic meningitis.

Most cases of eosinophilic meningitis due to A. cantonensis are self-limited and resolve without complications. However, neurologic sequelae do develop in some cases, and deaths have been reported from the disease.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
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Person-centred transition programme to empower adolescents with congenital heart disease in the transition to adulthood: a study protocol for a hybrid randomised controlled trial (STEPSTONES project)


When a young person grows up, they evolve from an independent child to an empowered adult. If an individual has a chronic condition, this additional burden may hamper adequate development and independence. Transition programmes for young persons with chronic disorders aim to provide the necessary skills for self-management and participation in care. However, strong evidence on the effects of these interventions is lacking. Therefore, as part of the STEPSTONES project (Swedish Transition Effects Project Supporting Teenagers with chrONic mEdical conditionS), we propose a trial to assess the effectiveness of a structured, person-centred transition programme to empower adolescents with congenital heart disease in the transition to adulthood.


STEPSTONES will use a hybrid experimental design in which a randomised controlled trial is embedded in a longitudinal, observational study. It will be conducted in 4 paediatric cardiology centres in Sweden. 2 centres will be allocated to the randomised controlled trial group, assigning patients randomly to the intervention group (n=63) or the comparison group (n=63). The other 2 centres will form the intervention-naïve control group (n=63). The primary outcome is the level of patient empowerment, as measured by the Gothenburg Young Persons Empowerment Scale (GYPES).

Ethics and dissemination

The study has been approved by the Regional Ethical Board of Gothenburg, Sweden. Findings will be reported following the CONSORT statement and disseminated at international conferences and as published papers in peer-reviewed journals.

Trial registration number

NCT02675361; pre-results.

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Optimal body fat percentage cut-off values for identifying cardiovascular risk factors in Mongolian and Han adults: a population-based cross-sectional study in Inner Mongolia, China


The present study was designed to determine the optimal cut-off values of body fat percentage (BF%) for the detection of cardiovascular disease (CVD) risk factors in Mongolian and Han adults.


This cross-sectional study involving 3221 Chinese adults (2308 Han and 913 Mongolian) aged 20–80 years was conducted in Inner Mongolia Autonomous Region, China, in 2014. Data from a standardised questionnaire, physical examination and blood sample were obtained. The BF% was estimated using bioelectrical impedance analysis. Optimal BF% cut-offs were analysed by receiver operating characteristic curves to predict the risk of diabetes, hypertension and dyslipidaemia. Binary logistic regression analysis was performed to evaluate the OR of each CVD risk factor according to obesity defined by BF%.


Mean BF% levels were lower in men than in women (22.54±5.77 vs 32.95±6.18 in Han, 23.86±5.72 vs 33.98±6.40 in Mongolian population, respectively; p<0.001). In Han population, the area under curve (AUC) values for BF% ranged from 0.589 to 0.699 for men and from 0.711 to 0.763 for women. Compared with men, AUCs for diabetes and clustering of ≥2 risk factors in women were significantly higher (p<0.05). The AUCs for BF% in women (0.685–0.783) were similar with those in men (0.686–0.736) for CVD risk factors in Mongolian population. In Han adults, the optimal BF% cut-off values to detect CVD risk factors varied from 18.7% to 24.2% in men and 32.7% to 35.4% in women. In Mongolian population, the optimal cut-off values of BF% for men and women ranged from 21.0% to 24.6% and from 35.7% to 40.0%, respectively. Subjects with high BF% (≥24% in men, ≥34% in women) had higher risk of CVD risk factors in Han (age-adjusted ORs from 1.479 to 3.680, 2.660 to 4.016, respectively). In Mongolia, adults with high BF% (≥25% in men, ≥35% in women) had higher risk of CVD risk factors (age-adjusted ORs from 2.587 to 3.772, 2.061 to 4.882, respectively).


The optimal BF% cut-offs for obesity for the prediction of CVD risk factors in Chinese men and women were approximately 24% and 34% for Han adults and 25% and 35% for Mongolian population of Inner Mongolia, China, respectively.

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Education achievement and type 2 diabetes--what mediates the relationship in older adults? Data from the ESTHER study: a population-based cohort study


The study aims to identify the mediating factors of the relationship between education achievement and incident type 2 diabetes mellitus (T2DM) in older adults.


Population-based cohort study.


Participants were recruited from the German federal state of Saarland.


Participants were excluded if they had prevalent T2DM or missing data on prevalent T2DM, missing or zero follow-up time for incident T2DM or were under 50 years of age. The total sample consisted of 7462 individuals aged 50–75 years (42.8% men, mean age 61.7 years) at baseline (2000–02). The median follow-up time was 8.0 years.


Cox proportional hazards regression was initially used to determine the direct association between education achievement and incident T2DM. Using the Baron and Kenny approach, we then investigated the associations between education achievement and incident T2DM with the potential mediators. The contribution of each of the putative mediating variables was then calculated.


A clear socioeconomic gradient was observed with regard to T2DM incidence with the lowest educated individuals at a greater risk of developing the disease during the follow-up period: HR (95% CI) high education: 0.52 (0.34 to 0.80); medium education: 0.80 (0.66 to 0.96). Seven of the variables considered explained a proportion of the education–T2DM relationship (body mass index, alcohol consumption, hypertension, fasting triglycerides, high-density lipoprotein (HDL) cholesterol, physical activity and smoking status), where the contribution of the variables ranged from 1.0% to 17.7%. Overall, the mediators explained 31.7% of the relationship.


By identifying the possible mediating factors of the relationship between education achievement and incident T2DM in older adults, the results of this study can be used to assist with the development of public health strategies that aim to reduce socioeconomic inequalities in T2DM.

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An eclosion hormone-like gene participates in the molting process of Palaemonid shrimp Exopalaemon carinicauda


Molting behavior is an important physiological process related to metamorphosis, growth, and reproduction in crustaceans. Previous studies indicated that the molting process was controlled by 20-hydroxyecdysone (20E) and upstream hormones, peptides, and environmental factors, which regulate 20E function. Eclosion hormone (EH) in insect is a kind of neuropeptide that is regulated by 20E and triggers ecdysis behavior at the end of molting process. However, the function of eclosion hormone gene during the molting process in crustaceans is still largely unknown. In the present study, an eclosion hormone-like gene EcEHL was identified from Exopalaemon carinicauda. The deduced amino acid sequence of EcEHL contained a signal peptide, a typical eclosion domain, and six conserved cysteine residues forming three putative disulfide bonds. EcEHL was predominantly expressed in the epidermis, gill, and eyestalk of shrimp. In situ hybridization analysis showed that EcEHL transcripts were localized in gill cells and in medulla externa X-organ, medulla terminalis X-organ, sinus gland, and lamina ganglionaris of eyestalks. During the molting process of shrimp, EcEHL showed the highest expression level in shrimp at the premolt stage. The expression level of EcEHL in shrimp at mid premolt stage was up-regulated by injection of exogenous 20E. Silencing of EcEHL using double-stranded RNA delayed both the molting process and ecdysis rate of E. carinicauda. Furthermore, injection of exogenous 20E to shrimp at mid premolt stage (D2) could remarkably speed up the molting process and also raise the ecdysis rate of E. carinicauda. The results revealed that EcEHL might participate in the molting process of shrimp and its expression was regulated by 20E. These data will help us to understand the molecular mechanism of molting in crustacean.

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Snowfall and myocardial infarction. What is the effect of barometric pressure? [Letters]

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Improving coverage of medical research in a changing media environment [Commentary]

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Conflicts of interest and expertise of independent commenters in news stories about medical research [Research]


Media coverage of medical research influences the views and behaviours of clinicians, scientists and members of the public. We examined how frequently commenters in news stories about medical research have relevant expertise and have academic and financial conflicts, how often such conflicts are reported and whether there are associations between the conflicts and the disposition of the comments toward the findings of the source research.


We analyzed 104 independent comments in news stories on original clinical research published in high-impact medical journals from Jan. 1 to Mar. 31, 2013, and 21 related journal editorials. Main outcomes were prevalence of relevant academic and clinical expertise, prevalence and reporting of academic and financial conflicts of interest, and disposition of comments toward study findings.


Only 1 in 6 news stories included independent comments. Overall, 25% of commenters and 0% of editorialists had neither relevant academic nor clinical expertise (p = 0.007). Among the 104 comments, an academic conflict of interest was present for 56 (54%), of which 25 (45%) were reported in the news stories. A financial conflict of interest was present for 33 (32%) of the comments, of which 11 (33%) were reported. When commenters’ conflicts of interest were congruent with the findings of the source research, 97% and 93% of comments associated with academic and financial conflicts of interest, respectively, were favourably disposed toward the research. These values were 16% and 17%, respectively, when the conflicts of interest were not congruent with the research findings.


Independent commenters in new stories about medical research may lack relevant academic or clinical expertise. Academic or financial conflicts of interest were frequently present among independent commenters but infrequently reported, and were often associated with the disposition of comments about the source research.

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Canada wins legal battle to set patent rules [News]

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Use of azithromycin and risk of ventricular arrhythmia [Research]


There are conflicting findings from observational studies of the arrhythrogenic potential of azithromycin. Our aim was to quantify the association between azithromycin use and the risk of ventricular arrhythmia.


We conducted a nested case–control study within a cohort of new antibiotic users identified from a network of 7 population-based health care databases in Denmark, Germany, Italy, the Netherlands and the United Kingdom for the period 1997–2010. Up to 100 controls per case were selected and matched by age, sex and database. Recency of antibiotic use and type of drug (azithromycin was the exposure of interest) at the index date (occurrence of ventricular arrhythmia) were identified. We estimated the odds of ventricular arrhythmia associated with current azithromycin use relative to current amoxicillin use or nonuse of antibiotics (≥ 365 d without antibiotic exposure) using conditional logistic regression, adjusting for confounders.


We identified 14 040 688 new antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed in 12 874, of whom 30 were current azithromycin users. The mean age of the cases and controls was 63 years, and two-thirds were male. In the pooled data analyses across databases, azithromycin use was associated with an increased risk of ventricular arrhythmia relative to nonuse of antibiotics (adjusted odds ratio [OR] 1.97, 95% confidence interval [CI] 1.35–2.86). This increased risk disappeared when current amoxicillin use was the comparator (adjusted OR 0.90, 95% CI 0.48–1.71). Database-specific estimates and meta-analysis confirmed results from the pooled data analysis.


Current azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication.

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Hot bodies; Cold War: the forgotten history of breast thermography [Humanities]

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Mumps in a 27-year-old man [Practice]

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Response to: "Snowfall and myocardial infarction. What is the effect of barometric pressure?" [Letters]

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Bamboo nodes of the vocal cords [Practice]

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Home visits to frail elderly can save money and angst [News]

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Safety and Efficacy of Brodalumab for Moderate-to-Severe Plaque Psoriasis: A Systematic Review and Meta-Analysis



Psoriasis is an inflammatory skin disease that affects 2–3% of the worldwide population. The interleukin-17 cytokine family has been proven to play a central role in the pathogenesis of psoriasis. Brodalumab is a novel biologic agent that targets interleukin-17 molecules and their receptors. We aimed to evaluate the safety and efficacy of brodalumab as a therapeutic agent for moderate-to-severe psoriasis in a meta-analysis framework.


A computer literature search of PubMed, OVID, Cochrane Central, EMBASE, EBSCO, Scopus, and Web of Science was conducted using relevant keywords. Data were extracted from eligible trials and analyzed using RevMan (Version 5.3 for windows) and OpenMeta [Analyst] software.


Six clinical trials (n = 4118 patients) were pooled in the final analysis. The pooled effect size favored brodalumab over placebo in terms of the Psoriasis Area and Severity Index (PASI) 75 [risk ratio (RR) = 12.61, 95% confidence interval (CI) 9.74–16.34], PASI 90 (RR = 28.72, 95% CI 18.34–44.98), and PASI 100 (RR = 61.23, 95% CI 25.48–147.17). Analysis of secondary outcomes showed that brodalumab was superior to placebo in terms of static physician's global assessment (RR = 32.53, 95% CI 13.80–76.69) and psoriasis symptoms inventory scores (RR = 14.70, 95% CI 8.38–25.78). Meta-regression analysis found a significant linear association between the brodalumab dose and the effect size on PASI and psoriasis symptoms inventory scores. The rate of overall adverse events was slightly higher in the brodalumab group (RR = 1.13, 95% CI 1.06–1.22); however, none of the individual adverse events were significantly higher in the brodalumab group, compared to the placebo group.


Brodalumab showed an acceptable safety profile and a robust efficacy in the treatment of moderate-to-severe plaque psoriasis. However, the current evidence is insufficient to confirm maintenance of these results in the long term; therefore, larger studies with longer follow-up periods are required.


Effects of maternal health anxiety on children’s health complaints, emotional symptoms, and quality of life


Little is known about family risk factors and intergenerational transmission of psychological disturbance in the development of health anxiety (HA). This study investigated HA and related concepts in 8- to 17-year-old children who had been exposed to different maternal health status. Using a family case–control design, three family groups were included: (1) 50 case children of mothers with severe (HA); (2) 49 control children of mothers with rheumatoid arthritis (RA); and (3) 51 control children of healthy mothers. Children and mothers completed a battery of standardised questionnaires. Case children reported significantly higher level of HA symptoms than children of mothers with RA but not compared to children of healthy mothers. There was no significant difference between the children's self-reports in the three groups with regard to anxiety symptoms in general, physical complaints, or quality of life. In contrast, mothers with HA reported their children as having more emotional and physical symptoms than mothers in one or both control groups. Compared to mothers with RA but not healthy mothers, mothers with HA also reported more visits to the general practitioner with their children during the past year. The findings suggest that maternal HA only weakly affects children's own report of HA and thereby may not be a strong risk factor for the development of HA symptoms in childhood. However, mothers with severe HA seem to conceive their children as more ill and present them more often in the health care system which could, therefore, be an important target for intervention in adult patients.


Dynamic Model of Spur Gear Pair with Modulation Internal Excitation

In the actual measurements, vibration and noise spectrum of gear pair often exhibits sidebands around the gear mesh harmonic orders. In this study, a nonlinear time-varying dynamic model of spur gear pair was established to predict the modulation sidebands caused by the AM-FM modulation internal excitation. Here, backlash, modulation time-varying mesh stiffness, and modulation transmission error are considered. Then the undamped natural mode was studied. Numerical simulation was made to reveal the dynamic characteristic of a spur gear under modulation condition. The internal excitation was shown to exhibit obvious modulation sideband because of the modulation time-varying mesh stiffness and modulation transmission error. The Runge-Kutta method was used to solve the equations for analyzing the dynamic characteristics with the effect of modulation internal excitation. The result revealed that the response under modulation excitation exhibited obvious modulation sideband. The response under nonmodulation condition was also calculated for comparison. In addition, an experiment was done to verify the prediction of the modulation sidebands. The calculated result was consistent with the experimental result.

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Esthetic Rehabilitation with Direct Composite Veneering: A Report of 2 Cases

Esthetic or cosmetic dentistry is one of the main areas of dental practice. Increasing demand of patients for esthetics has resulted in the development of several techniques for restoring the anterior teeth. Composite resin restorations have become an integral part of contemporary restorative dentistry and can be called “star of minimal invasion” due to its conservative concepts. The direct composite veneering allows restoring the tooth in a natural way and preservation of sound tooth structure when compared to indirect restorations. This article presents two case reports of esthetic rehabilitation of anterior teeth using direct composite veneering with two-year follow-up with acceptable outcome.

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Osteomyelitis of the Patella in a 10-Year-Old Girl: A Case Report and Review of the Literature

The incidence of osteomyelitis constantly declines. While the disease most commonly affects the long bones, involvement of the patella is rarely seen. Due to this rarity and the variable clinical presentation, diagnosis is often delayed. The present case report describes a 10-year-old female patient with a delayed diagnosis of patella osteomyelitis. The diagnostic procedures and the treatment regimen are described. Additionally, a detailed literature review of the available publications reporting osteomyelitis of the patella in children is presented.

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Physicochemical Characterization of Representative Firewood Species Used for Cooking in Some Colombian Regions

Socioeconomic conditions and the main firewood species used for cooking in three Colombian regions are studied in this work. The species collected were Cordia alliodora, Guazuma ulmifolia, Eucalyptus grandis, and Pinus patula. The used patterns of biomass and socioeconomic conditions of the selected regions were defined by means of secondary information. Firewood was physicochemically characterized and the species are compared with fossil fuels with regard to emissions of CO2, energy density, and costs. The studied regions require solutions to use firewood in eco-efficient systems, since in these rural regions people use biomass as an energy source. Studied firewood species are suitable to be gasified in fixed bed reactors due to their high volatile matter content (>80%) and low ash content (

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Validation of the Decomposition Method for Fast MIMO Over-the-Air Measurements

Over-the-air (OTA) throughput tests of wireless Multiple-Input Multiple-Output (MIMO) devices are an important tool for network operators and manufacturers. The user equipment (UE) is placed in an anechoic chamber and a random fading process is emulated by a base-station emulator (BSE). The antenna characteristic of the UE is taken into account by sampling the sphere around the UE with the BSE test antenna at a large number of positions. For low-variance throughput results, long measurement intervals over many fading realizations are required, leading to long and expensive measurement periods in an anechoic chamber. To speed up the OTA test, we analyze the Decomposition Method (DM). The DM splits the throughput measurement into two parts: (1) a receiver algorithm performance tests taking the fading process into account and (2) an antenna performance test without fading process emulation. Both results are combined into a single throughput estimate. The DM allows for a measurement time reduction of more than one order of magnitude. We provide an analytic and numerical analysis as well as measurements. Our detailed results show the validity of the DM in all practical settings.

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Synthesis Approaches of Zinc Oxide Nanoparticles: The Dilemma of Ecotoxicity

Human’s quest for innovation, finding solutions of problems, and upgrading the industrial yield with energy efficient and cost-effective materials has opened the avenues of nanotechnology. Among a variety of nanoparticles, zinc oxide nanoparticles (ZnO) have advantages because of the extraordinary physical and chemical properties. It is one of the cheap materials in cosmetic industry, nanofertilizers, and electrical devices and also a suitable agent for bioimaging and targeted drug and gene delivery and an excellent sensor for detecting ecological pollutants and environmental remediation. Despite inherent toxicity of nanoparticles, synthetic routes are making use of large amount of chemical and stringent reactions conditions that are contributing as environmental contaminants in the form of high energy consumption, heat generation, water consumption, and chemical waste. Further, it is also adding to the innate toxicity of nanoparticles (NPs) that is either entirely ignored or poorly investigated. The current review illustrates a comparison between pollutants and hazards spawned from chemical, physical, and biological methods used for the synthesis of ZnO. Further, the emphasis is on devising eco-friendly techniques for the synthesis of ZnO especially biological methods which are comparatively less hazardous and need to be optimized by controlling the reaction conditions in order to get desired yield and characteristics.

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Design of RMPC for Boiler Superheated Steam Temperature Based on Memoryless Feedback Multistep Strategy

The collection of superheated steam temperature models of a thermal power plant under different loads can be approximated to “multimodel” linear uncertain systems. After transformation, the tracking system was obtained from “multimodel” linear uncertain systems. For this tracking uncertain system, a mixed robust model predictive control (HRMPC) based on a memoryless feedback multistep strategy is proposed. A multistep control strategy combines the advantages of predictive control rolling optimization with memoryless feedback control thoughts. It could effectively decrease the controller optimization parameter and ensure closed-loop system stability, and, at the same time, it also achieved acceptable control performance. Successful application to the superheated steam temperature system of a 300 MW thermal power plant verified the study of the HRMPC-P cascade controller design scheme in terms of feasibility and effectiveness.

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Experimental Study on Friction Sliding Performance of Rubber Bearings in Bridges

To fully ascertain the ultimate shear failure state and the friction sliding performance of laminated rubber bearings in bridges, a series of cyclic loading tests were conducted. The energy dissipation characteristics of the laminated rubber bearings with two end plates, rubber bearings with unilateral friction sliding, and lead rubber bearing (LRB) under low-frequency cyclic loads were compared and analyzed. The results showed the following. () The ultimate shear deformation of the rubber bearings with two end plates could reach 300% to 400% of the rubber layer thickness. The energy dissipation capacity of the bearings was weak, and the hysteresis curves presented narrow zonal shapes. () The rubber bearings with unilateral friction sliding had similar energy dissipation capacities compared to the LRB. With the increase of the sliding distance, the dissipated energy continuously enlarged. The shear deformation of the bearing was no longer increased after reaching the maximum. After the test, the bearings remained in a good condition. The hysteresis curves of the load and displacement presented bilinear shapes. () Under the cyclic loading, the energy dissipation capacity of LRB was stable. The hysteresis curves of LRB were always fuller than the laminated rubber bearings.

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Study on the Correlation of Vibration Properties and Crack Index in the Health Assessment of Tunnel Lining

This paper examines the correlation of vibration properties and crack index of tunnel lining in evaluating risk of collapsing. The visual inspection method, which was widely used, was not reliable enough as the stability of tunnel lining was influenced by the voids and the cracks that were invisible. A new method for the health assessment of tunnel lining was proposed, which can evaluate the whole structural condition according to the vibration properties of tunnel lining. A series of field tests were conducted to evaluate the validity of this new method and to make a comparative analysis with the visual inspection test results. The resultant average spectrum (RAS) of tunnel lining was identified according to the acceleration data of ambient vibration test of Hidake Tunnel in Japan. The tunnel lining crack index (TCI) was also obtained by digital visual inspection test. The correlation between the vibration characteristics and the crack index of tunnel lining was confirmed. However, the voids and the cracks on the inside of the lining were neglected in visual inspection test, which could pose a serious threat to tunnel safety. The vibration measurements by seismometer are an effective way to evaluate the global stability of tunnel lining.

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A Mesoscopic Simulation for the Early-Age Shrinkage Cracking Process of High Performance Concrete in Bridge Engineering

On a mesoscopic level, high performance concrete (HPC) was assumed to be a heterogeneous composite material consisting of aggregates, mortar, and pores. The concrete mesoscopic structure model had been established based on CT image reconstruction. By combining this model with continuum mechanics, damage mechanics, and fracture mechanics, a relatively complete system for concrete mesoscopic mechanics analysis was established to simulate the process of early-age shrinkage cracking in HPC. This process was based on the dispersion crack model. The results indicated that the interface between the aggregate and mortar was the crack point caused by shrinkage cracks in HPC. The locations of early-age shrinkage cracks in HPC were associated with the spacing and the size of the aggregate particle. However, the shrinkage deformation size of the mortar was related to the scope of concrete cracking and was independent of the crack position. Whereas lower water to cement ratios can improve the early strength of concrete, this ratio cannot control early-age shrinkage cracks in HPC.

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Preclinical characterization of BET family bromodomain inhibitor ABBV-075 suggests combination therapeutic strategies

ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered Phase I clinical trials. Comprehensive preclinical characterization of ABBV-075 demonstrated broad activity across cell lines and tumor models representing a variety of hematological malignancies and solid tumor indications. In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent G1 cell cycle arrest without extensive apoptosis. In this study, we show that ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) cells. Apoptosis induced by ABBV-075 was mediated in part by modulation of the intrinsic apoptotic pathway, exhibiting synergy with the BCL-2 inhibitor venetoclax in preclinical models of AML. In germinal center diffuse large B cell lymphoma, BCL-2 levels or venetoclax sensitivity predicted the apoptotic response to ABBV-075 treatment. In vivo combination studies uncovered surprising benefits of low doses of ABBV-075 coupled with bortezomib and azacitidine treatment, despite the lack of in vitro synergy between ABBV-075 and these agents. The in vitro/in vivo activities of ABBV-075 described here may serve as a useful reference to guide the development of ABBV-075 and other BET family inhibitors for cancer therapy.

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Locoregional effects of microbiota in a preclinical model of colon carcinogenesis

Inflammation and microbiota are critical components of intestinal tumorigenesis. To dissect how the microbiota contributes to tumor distribution, we generated germ-free (GF) ApcMin/+ and ApcMin/+;Il10-/- mice and exposed them to specific-pathogen-free (SPF) or colorectal cancer-associated bacteria. We found colon tumorigenesis significantly correlated with inflammation in SPF housed ApcMin/+;Il10-/-, but not ApcMin/+ mice. In contrast, small intestinal neoplasia development significantly correlated with age in both ApcMin/+;Il10-/- and ApcMin/+ mice. GF ApcMin/+;Il10-/- mice conventionalized by an SPF microbiota had significantly more colon tumors compared to GF mice. Gnotobiotic studies revealed that while Fusobacterium nucleatum clinical isolates with FadA and Fap2 adhesins failed to induce inflammation and tumorigenesis, pks+ Escherichia coli promoted tumorigenesis in the ApcMin/+;Il10-/- model in a colibactin-dependent manner, suggesting colibactin is a driver of carcinogenesis. Our results suggest a distinct etiology of cancers in different locations of the gut, where colon cancer is primarily driven by inflammation and the microbiome, while age is a driving force for small intestine cancer.

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NRF2 induction supporting breast cancer cell survival is enabled by oxidative stress-induced DPP3-KEAP1 interaction

NRF2 is a transcription factor serving as a master regulator of the expression of many genes involved in cellular responses to oxidative and other stresses. In the absence of stress, NRF2 is constantly synthesized but maintained at low levels as it is targeted by KEAP1 for ubiquitination and proteasome-mediated degradation. NRF2 binds KEAP1 mainly through a conserved "ETGE" motif that has also been found in several other proteins, such as DPP3, which has been shown to bind KEAP1 and enhance NRF2 function upon overexpression. Here we demonstrate the interaction between endogenous DPP3 and endogenous KEAP1. We further show that the DPP3-KEAP1 interaction is strongly induced by hydrogen peroxide and that DPP3 is required for timely NRF2 induction and nuclear accumulation in the estrogen receptor (ER)-positive MCF7 breast cancer cells. Moreover, we present evidence that the binding of DPP3 to KEAP1 stabilizes the latter. Finally, we show that DPP3 is overexpressed in breast cancer and that elevated levels of DPP3 mRNA correlate with increased NRF2 downstream gene expression and poor prognosis, particularly for ER-positive breast cancer. Our studies reveal novel insights into the regulation of NRF2 and identify DPP3 and an NRF2 transcriptional signature as potential biomarkers for breast cancer prognosis and treatment.

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Activation of NOTCH signaling by tenascin-C promotes growth of human brain tumor-initiating cells

Elevated NOTCH signaling is implicated in tumorigenesis. The brain tumor- initiating cells (BTICs) present in malignant glioma exhibit elevated NOTCH activity but the mechanism of this activation is unknown. Here, we provide evidence that tenascin-C (TNC), an extracellular matrix protein prominent in malignant glioma, increases NOTCH activity in BTICs to promote their growth. We demonstrate the proximal localization of TNC and BTICs in human glioblastoma specimens, and in the brains of mice implanted with human BTIC intracranial xenografts. In culture, TNC was superior amongst several extracellular matrix proteins in enhancing the sphere-forming capacity of glioma patient-derived BTICs. Exogenously applied or autocrine TNC increased BTIC growth through an α2β1 integrin-mediated mechanism that elevated the NOTCH ligand, Jagged1 (JAG1). Microarray analyses and confirmatory PCR and Western blots in BTICs found that components of the NOTCH signaling pathway, including JAG1, ADAMTS15 and NICD1/2 were elevated in BITCs after TNC exposure. Inhibition of gamma secretase and metalloproteinase proteolysis in the NOTCH pathway, or knockdown of α2β1 integrin or JAG1, reduced the proliferative effect of TNC on BTIC. Collectively, our study has several novelties: the identification of TNC as a key initiator of the elevated NOTCH signaling in BTICs; the discovery that a prominent ECM component in malignant gliomas, TNC, is a promoter of BTIC growth; and the establishment of the TNC- α2β1 integrin - JAG1-NOTCH axis as a candidate for therapeutic interventions to improve the prognosis of patients with malignant glioma.

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Metabolic Markers and Statistical Prediction of Serous Ovarian Cancer Aggressiveness by Ambient Ionization Mass Spectrometry Imaging

Ovarian high-grade serous carcinoma (HGSC) results in the highest mortality among gynecological cancers, developing rapidly and aggressively. Dissimilarly, serous borderline ovarian tumors (BOT) can progress into low-grade serous carcinomas and have relatively indolent clinical behavior. The underlying biological differences between HGSC and BOT call for accurate diagnostic methodologies and tailored treatment options, and identification of molecular markers of aggressiveness could provide valuable biochemical insights and improve disease management. Here we used desorption electrospray ionization (DESI) mass spectrometry (MS) to image and chemically characterize the metabolic profiles of HGSC, BOT, and normal ovarian tissue samples. DESI-MS imaging enabled clear visualization of fine papillary branches in serous BOT and allowed for characterization of spatial features of tumor heterogeneity such as adjacent necrosis and stroma in HGSC. Predictive markers of cancer aggressiveness were identified, including various free fatty acids, metabolites, and complex lipids such as ceramides, glycerophosphoglycerols, cardiolipins, and glycerophosphocholines. Classification models built from a total of 89,826 individual pixels, acquired in positive and negative ion modes from 78 different tissue samples, enabled diagnosis and prediction of HGSC and all tumor samples in comparison to normal tissues, with overall agreements of 96.4% and 96.2%, respectively. HGSC and BOT discrimination was achieved with an overall accuracy of 93.0%. Interestingly, our classification model allowed identification of three BOT samples presenting unusual histologic features that could be associated with the development of low-grade carcinomas. Our results suggest DESI-MS as a powerful approach for rapid serous ovarian cancer diagnosis based on altered metabolic signatures.

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Targeting autocrine CCL5-CCR5 axis reprograms immunosuppressive myeloid cells and reinvigorates antitumor immunity

The tumor-promoting potential of CCL5 has been proposed but remains poorly understood. We demonstrate here that an autocrine CCL5-CCR5 axis is a major regulator of immunosuppressive myeloid cells (IMC) of both monocytic and granulocytic lineages. The absence of the autocrine CCL5 abrogated the generation of granulocytic myeloid-derived suppressor cells and tumor-associated macrophages. In parallel, enhanced maturation of intratumoral neutrophils and macrophages occurred in spite of tumor-derived CCL5. The refractory nature of ccl5-null myeloid precursors to tumor-derived CCL5 was attributable to their persistent lack of membrane-bound CCR5. The changes in the ccl5-null myeloid compartment subsequently resulted in increased tumor-infiltrating cytotoxic CD8+ T cells and decreased regulatory T cells in tumor-draining lymph nodes. An analysis of human triple-negative breast cancer specimens demonstrated an inverse correlation between "immune CCR5" levels and the maturation status of tumor-infiltrating neutrophils as well as 5-year-survival rates. Targeting the host CCL5 in bone marrow via nanoparticle-delivered expression silencing, in combination with the CCR5 inhibitor Maraviroc, resulted in strong reductions of IMC and robust anti-tumor immunities. Our study suggests that the myeloid CCL5-CCR5 axis is an excellent target for cancer immunotherapy.

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A squalene-based nanomedicine for oral treatment of colon cancer

Nanotechnology offers many possibilities to improve drug treatments, including with regard to drug pharmacology. The current study reports a simple approach to improve cisplatin efficacy in the treatment of colon cancer through the creation of orally administered squalenoylated nanoparticles loaded with cisplatin (SQ-CDDP NP). Cytotoxic effects of SQ-CDDP NP were assessed in human colonic cells and in mouse models of intestinal cancer. In cell culture, SQ-CDDP NP exhibited at least 10-fold greater cytotoxic potency compared to uncomplexed cisplatin, reflecting an enhancement in intracellular accumulation and DNA platination. Mechanistic investigations showed that SQ-CDDP NP stimulated ROS production, expression of heavy metals-inducible and stress-inducible genes, stress kinase cascades and apoptosis. In ApcMin/+ mice, a model of intestinal tumorigenesis, oral administration of SQ-CDDP NP curtailed spontaneous tumor formation and azoxymethane-induced colon carcinogenesis with no apparent evidence of tissue toxicity. Our results offer preclinical validation of a nanocarrier formulation that can safely improve chemotherapeutic efficacy, address risks of drug resistance, and improve patient compliance by enabling oral administration.

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SSRP1 cooperates with PARP and XRCC1 to facilitate single strand DNA break repair by chromatin priming

DNA single strand breaks (SSB) are the most common form of DNA damage, requiring repair processes that to initiate must overcome chromatin barriers. The FACT complex comprised of the SSRP1 and SPT16 proteins are important for maintaining chromatin integrity, with SSRP1 acting as an histone H2A/H2B chaperone in chromatin disassembly during DNA transcription, replication and repair. In this study, we show that SSRP1 but not SPT16 is critical for cell survival after ionizing radiation or methyl methanesulfonate-induced single-strand DNA damage. SSRP1 is recruited to SSB in PARP-dependent manner and retained at DNA damage sites by N-terminal interactions with the DNA repair protein XRCC1. Mutational analyses showed how SSRP1 function is essential for chromatin decondensation and histone H2B exchange at sites of DNA strand breaks, which are both critical to prime chromatin for efficient SSB repair and cell survival. By establishing how SSRP1 facilitates SSB repair, our findings provide a mechanistic rationale to target SSRP1 as a general approach to selectively attack cancer cells.

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Western diet deregulates bile acid homeostasis, cell proliferation and tumorigenesis in colon

Western-style diets (WD) high in fat and scarce in fiber and vitamin D increase risks of colorectal cancer (CRC). Here we performed a long-term diet study in mice to follow tumorigenesis and characterize structural and metabolic changes in colon mucosa associated with WD and predisposition to CRC. WD increased colon tumor numbers and mucosa proteomic analysis indicated severe deregulation of intracellular bile acid (BA) homeostasis and activation of cell proliferation. WD also increased crypt depth and colon cell proliferation. Despite increased luminal BA, colonocytes from WD-fed mice exhibited decreased expression of the BA transporters FABP6, OSTβ and ASBT and decreased concentrations of secondary BA deoxycholic acid and lithocholic acid, indicating reduced activity of the nuclear BA receptor FXR. Overall, our results suggest that WD increases cancer risk by FXR inactivation leading to BA deregulation and increased colon cell proliferation.

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SFK/FAK signaling attenuates osimertinib efficacy in both drug-sensitive and drug-resistant models of EGFR-mutant lung cancer

Mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as osimertinib, are active agents for the treatment of EGFR-mutant lung cancer. Specifically, these agents can overcome the effects of the T790M mutation, which mediates resistance to first and second-generation EGFR TKI, and recent clinical trials have documented their efficacy in patients with EGFR-mutant lung cancer. Despite promising results, therapeutic efficacy is limited by development of acquired resistance. Here we report that Src family kinases (SFK) and focal adhesion kinase (FAK) sustain AKT and mitogen-activated protein kinase (MAPK) pathway signaling under continuous EGFR inhibition in osimertinib sensitive cells. Inhibiting either the MAPK pathway or the AKT pathway enhanced the effects of osimertinib. Combined SFK/FAK inhibition exhibited the most potent effects on growth inhibition, induction of apoptosis, and delay of acquired resistance. SFK family member YES1 was amplified in osimertinib- resistant EGFR-mutant tumor cells, the effects of which were overcome by combined treatment with osimertinib and SFK inhibitors. In conclusion, our data suggest that concomitant inhibition of both SFK/FAK and EGFR may be a promising therapeutic strategy for EGFR-mutant lung cancer.

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NOTCH1 Signaling Regulates Self-renewal and Platinum Chemoresistance of Cancer Stem-like Cells in Human Non-small Cell Lung Cancer

Cancer stem-like cells (CSC) are thought to drive tumor initiation, metastasis, relapse and therapeutic resistance, but their specific pathogenic characters in many cancers including non-small cell lung cancer (NSCLC) have yet to be well defined. Here we develop findings that the growth factor HGF promotes CSC sphere formation in NSCLC cell populations. In patient-derived sphere-forming assays (PD-SFA) with HGF, CD49f and CD104 were defined as novel markers of lung CSC (LCSC). In particular, we isolated a subpopulation of CD166+CD49fhiCD104-Lin- LCSC present in all human specimens of NSCLC examined, regardless of their histological subtypes or genetic driver mutations. This specific cell population was tumorigenic and capable of self-renewal, giving rise to tumor spheres in vitro and orthotopic lung tumors in immune-compromised mice. Mechanistic investigations established that NOTCH1 was preferentially expressed in this cell subpopulation and required for self-renewal via the transcription factor HES1. Through a distinct HES1-independent pathway, NOTCH1 also protected LCSCs from cisplatin-induced cell death. Notably, treatment with a γ-secretase inhibitor that blunts NOTCH1 function ablated self-renewing LCSC activity and restored platinum sensitivity in vitro and in vivo. Overall, our results define the pathogenic characters of a cancer stem-like subpopulation in lung cancer, the targeting of which may relieve platinum resistance in this disease.

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The Clinical Indications for Limited Surgery of Intraductal Papillary Mucinous Neoplasms of the Pancreas



There are many reports about limited surgery for intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. However, there is no consensus on limited surgery for IPMNs. The primary objective of this study was to define the clinical indications for limited surgery for IPMNs.


The data of 98 patients who underwent curative resections for IPMN were retrospectively analyzed. IPMNs were classified into four different pathological grades: low-grade dysplasia (LGD), intermediate-grade dysplasia (IGD), high-grade dysplasia (HGD), and invasive carcinoma (Inv-IPMN). Inv-IPMNs were divided into T1a, T1b, and T1c or over T1c (≥T1c). Based on preoperative radiological findings, IPMNs were stratified into the three groups using the 2012 International Consensus Guidelines: worrisome features, high-risk stigmata (HRS), and others.


There were no positive lymph node cases and no recurrent cases of LGDs, IGDs, and HGDs. On the other hand, positive lymph node cases in T1a, T1b, and ≥T1c were seen in 37.5, 20, and 22.2% of cases, respectively. The recurrence rates of T1a, T1b, and ≥T1c were 50, 40, and 55.6%, respectively. Of the HRS cases, 30 (73.2%) were malignant and 25 (61%) were Inv-IPMN. HRS showed sensitivity of 92.6%, specificity of 77.5%, and accuracy of 81.6% to identify Inv-IPMN by preoperative imaging.


Limited surgery such as parenchyma-sparing pancreatectomy should be avoided for all cases of Inv-IPMNs, because every Inv-IPMN including T1a has the potential for lymph node metastasis and recurrence. HRS had high preoperative diagnostic ability for predicting Inv-IPMN. For cases that meet HRS criteria, pancreatectomy with lymphadenectomy is needed, and limited surgery should be withheld.


Clinicopathological Characteristics and Prognostic Factors of Patients with Siewert Type II Esophagogastric Junction Carcinoma: A Retrospective Multicenter Study: Reply


ECLS in Trauma: Practical Application and a Review of Current Status


Extracorporeal life support has evolved considerably over the past two decades. Once considered as salvage or experimental therapy in adults, extracorporeal membrane oxygenation (ECMO) is evolving into a mainstream treatment for adult critical care. This is especially true in trauma and high-risk surgical patients, who have traditionally been excluded from consideration. Several technological advances have made this possible. This includes anticoagulant-bonded circuits, device miniaturization, servo-regulated centrifugal systems, and more efficient oxygenators. Adult ECMO may now be rapidly deployed for severe acute respiratory distress syndrome (ARDS) and cardiogenic shock. Trauma and surgical patients with severe ARDS should be considered for ECMO early in their clinical course to provide optimal lung rest.


Should Gastric Decompression Be a Routine Procedure in Patients Who Undergo Pylorus-Preserving Pancreatoduodenectomy?: Reply


The Totally Implantable Venous Access Device with Occurrence of Pneumothorax Still Remains an Issue


A Multispecialty Evaluation of Thiel Cadavers for Surgical Training



Changes in UK legislation allow for surgical procedures to be performed on cadavers. The aim of this study was to assess Thiel cadavers as high-fidelity simulators and to examine their suitability for surgical training.


Surgeons from various specialties were invited to attend a 1 day dissection workshop using Thiel cadavers. The surgeons completed a baseline questionnaire on cadaveric simulation. At the end of the workshop, they completed a similar questionnaire based on their experience with Thiel cadavers. Comparing the answers in the pre- and post-workshop questionnaires assessed whether using Thiel cadavers had changed the surgeons' opinions of cadaveric simulation.


According to the 27 participants, simulation is important for surgical training and a full-procedure model is beneficial for all levels of training. Currently, there is dissatisfaction with existing models and a need for high-fidelity alternatives. After the workshop, surgeons concluded that Thiel cadavers are suitable for surgical simulation (p = 0.015). Thiel were found to be realistic (p < 0.001) to have reduced odour (p = 0.002) and be more cost-effective (p = 0.003). Ethical constraints were considered to be small.


Thiel cadavers are suitable for training in most surgical specialties.


Treating Pilonidal Disease: You Do Not Need to Detonate a Naval Mine to Catch a Fish


An Evaluation of Preparedness, Delivery and Impact of Surgical and Anesthesia Care in Madagascar: A Framework for a National Surgical Plan



The Lancet Commission on Global Surgery (LCoGS) described the lack of access to safe, affordable, timely surgical, and anesthesia care. It proposed a series of 6 indicators to measure surgery, accompanied by time-bound targets and a template for national surgical planning. To date, no sub-Saharan African country has completed and published a nationwide evaluation of its surgical system within this framework.


Mercy Ships, in partnership with Harvard Medical School and the Madagascar Ministry of Health, collected data on the 6 indicators from 22 referral hospitals in 16 out of 22 regions of Madagascar. Data collection was by semi-structured interviews with ministerial, medical, laboratory, pharmacy, and administrative representatives in each region. Microsimulation modeling was used to calculate values for financial indicators.


In Madagascar, 29% of the population can access a surgical facility within 2 h. Surgical workforce density is 0.78 providers per 100,000 and annual surgical volume is 135–191 procedures per 100,000 with a perioperative mortality rate of 2.5–3.3%. Patients requiring surgery have a 77.4–86.3 and 78.8–95.1% risk of incurring impoverishing and catastrophic expenditure, respectively. Of the six LCoGS indicator targets, Madagascar meets one, the reporting of perioperative mortality rate.


Compared to the LCoGS targets, Madagascar has deficits in surgical access, workforce, volume, and the ability to offer financial risk protection to surgical patients. Its perioperative mortality rate, however, appears better than in comparable countries. The government is committed to improvement, and key stakeholder meetings to create a national surgical plan have begun.


TRP channels in brown and white adipogenesis from human progenitors: new therapeutic targets and the caveats associated with the common antibiotic, streptomycin [Research]

Transient receptor potential (TRP) channels are polymodal cell sensors responding to diverse stimuli and widely implicated in the developmental programs of numerous tissues. The evidence for an involvement of TRP family members in adipogenesis, however, is scant. We present the first comprehensive expression profile of all known 27 human TRP genes in mesenchymal progenitors cells during white or brown adipogenesis. Using positive trilineage differentiation as an exclusion criterion, TRP polycystic (P)3, and TPR melastatin (M)8 were found to be uniquely adipospecific. Knockdown of TRPP3 repressed the expression of the brown fat signature genes uncoupling protein (UCP)-1 and peroxisome proliferator-activated receptor coactivator (PGC)-1α as well as attenuated forskolin-stimulated uncoupled respiration. However, indices of generalized adipogenesis, such as lipid droplet morphology and fatty acid binding protein (FAPB)-4 expression, were not affected, indicating a principal mitochondrial role of TRPP3. Conversely, activating TRPM8 with menthol up-regulated UCP-1 expression and augmented uncoupled respiration predominantly in white adipocytes (browning), whereas streptomycin antagonized TRPM8-mediated calcium entry, downregulated UCP-1 expression, and mitigated uncoupled respiration; menthol was less capable of augmenting uncoupled respiration (thermogenesis) in brown adipocytes. TRPP3 and TRPM8 hence appear to be involved in the priming of mitochondria to perform uncoupled respiration downstream of adenylate cyclase. Our results also underscore the developmental caveats of using antibiotics in adipogenic studies.—Goralczyk, A., van Vijven, M., Koch, M., Badowski, C., Yassin, M. S., Toh, S.-A., Shabbir, A., Franco-Obregón, A., Raghunath, M. TRP channels in brown and white adipogenesis from human progenitors: new therapeutic targets and the caveats associated with the common antibiotic, streptomycin.

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A TSPO ligand attenuates brain injury after intracerebral hemorrhage [Research]

Intracerebral hemorrhage (ICH) is a devastating disease without effective treatment. After ICH, the immediate infiltration of leukocytes and activation of microglia are accompanied by a rapid up-regulation of translocator protein 18 kDa (TSPO). TSPO ligands have shown anti-inflammatory and neuroprotective properties in models of CNS injury. In this study, we determined the impact of a TSPO ligand, etifoxine, on brain injury and inflammation in 2 mouse models of ICH. TSPO was up-regulated in Iba1+ cells from brains of patients with ICH and in CD11b+CD45int cells from mice subjected to collagenase-induced ICH. Etifoxine significantly reduced neurodeficits and perihematomal brain edema after ICH induction by injection of either autologous blood or collagenase. In collagenase-induced ICH mice, the protection of etifoxine was associated with reduced leukocyte infiltration into the brain and microglial production of IL-6 and TNF-α. Etifoxine improved blood–brain barrier integrity and diminished cell death. Notably, the protective effect of etifoxine was abolished in mice depleted of microglia by using a colony-stimulating factor 1 receptor inhibitor. These results indicate that the TSPO ligand etifoxine attenuates brain injury and inflammation after ICH. TSPO may be a viable therapeutic target that requires further investigations in ICH.—Li, M., Ren, H., Sheth, K. N., Shi, F.-D., Liu, Q. A TSPO ligand attenuates brain injury after intracerebral hemorrhage.

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An eclosion hormone-like gene participates in the molting process of Palaemonid shrimp Exopalaemon carinicauda


Molting behavior is an important physiological process related to metamorphosis, growth, and reproduction in crustaceans. Previous studies indicated that the molting process was controlled by 20-hydroxyecdysone (20E) and upstream hormones, peptides, and environmental factors, which regulate 20E function. Eclosion hormone (EH) in insect is a kind of neuropeptide that is regulated by 20E and triggers ecdysis behavior at the end of molting process. However, the function of eclosion hormone gene during the molting process in crustaceans is still largely unknown. In the present study, an eclosion hormone-like gene EcEHL was identified from Exopalaemon carinicauda. The deduced amino acid sequence of EcEHL contained a signal peptide, a typical eclosion domain, and six conserved cysteine residues forming three putative disulfide bonds. EcEHL was predominantly expressed in the epidermis, gill, and eyestalk of shrimp. In situ hybridization analysis showed that EcEHL transcripts were localized in gill cells and in medulla externa X-organ, medulla terminalis X-organ, sinus gland, and lamina ganglionaris of eyestalks. During the molting process of shrimp, EcEHL showed the highest expression level in shrimp at the premolt stage. The expression level of EcEHL in shrimp at mid premolt stage was up-regulated by injection of exogenous 20E. Silencing of EcEHL using double-stranded RNA delayed both the molting process and ecdysis rate of E. carinicauda. Furthermore, injection of exogenous 20E to shrimp at mid premolt stage (D2) could remarkably speed up the molting process and also raise the ecdysis rate of E. carinicauda. The results revealed that EcEHL might participate in the molting process of shrimp and its expression was regulated by 20E. These data will help us to understand the molecular mechanism of molting in crustacean.


Overview of Coronary Heart Disease Risk Initiatives in South Asia


Purpose of Review

Cardiovascular disease (CVD) is now the leading cause of morbidity and mortality worldwide. Industrialization and economic growth have led to an unprecedented increment in the burden of CVD and their risk factors in less industrialized regions of the world. While there are abundant data on CVD and their risk factors from longitudinal cohort studies done in the West, good-quality data from South Asia are lacking.

Recent Findings

Several multi-institutional, observational, prospective registries, and epidemiologic cohorts in South Asia have been established to systematically evaluate the burden of CVD and their risk factors. The PINNACLE (Practice Innovation and Clinical Excellence) India Quality Improvement Program (PIQIP), the Kerala Acute Coronary Syndrome (ACS), and Trivandrum Heart Failure registries have focused on secondary prevention of CVD and performance measurement in both outpatient and inpatient settings, respectively. The Prospective Urban and Rural Epidemiology (PURE), Centre for Cardiometabolic Risk Reduction in South Asia (CARRS), and other epidemiologic and genetic studies have focused on primary prevention of CVD and evaluated variables such as environment, smoking, physical activity, health systems, food and nutrition policy, dietary consumption patterns, socioeconomic factors, and healthy neighborhoods.


The international cardiovascular community has been responsive to a burgeoning cardiovascular disease burden in South Asia. Several collaborations have formed between the West (North America in particular) and South Asia to catalyze evidence-based and data-driven changes in the federal health policy in this part of the world to promote cardiovascular health and mitigate cardiovascular risk.

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Clinical study of children with Takayasu arteritis: a retrospective study from a single center in China



Delayed diagnosis of childhood Takayasu arteritis (TA) is common due to its atypical symptoms. The objective of the present study was to summarize the clinical features of childhood TA to raise awareness and improve management.


Eleven children diagnosed with TA at our hospital were enrolled. Clinical information, diagnosis, treatment, and outcome were then examined retrospectively. The Pediatric Vasculitis Activity Score (PVAS) and the Indian Takayasu Clinical Activity Score (ITAS2010) were used to assess disease activity.


Male-to-female ratio was 4:7. The mean age was 9.4 (1.4–14) years and the average time to diagnosis was 40.6 days (12–90 days). All patients suffered from hypertension and few had immunologic abnormalities. Two patients had low levels of autoantibodies and one had elevated immunoglobulin E levels. Aberrant (elevated) laboratory parameters included erythrocyte sedimentation rate (ESR) (9/10 patients, 90.0%), protein excretion (8/9 patients, 88.9%), renin-angiotensin-aldosterone system (RAAS) activity (5/5 patients, 100.0%), and serum lipid levels (3/5 patients, 60%). The common onset patterns were headache with convulsions (27.2%) and kidney damage (27.2%). The abdominal aorta (81.8%) and renal artery (72.7%) were the most commonly involved vessels. At presentation, the mean PVAS and ITAS2010 scores were 12.1 (6–26)/63 and 9.7 (5–14)/57, respectively. All patients were treated with glucocorticoids and antihypertensive agents; two underwent renal artery stent placement.


The diagnosis of TA should be considered in patients with pediatric hypertension and high expression of inflammatory markers or abnormal urine results. Doppler ultrasonography of major vessels may be helpful. PVAS and ITAS2010 both help to evaluate disease activity, and the PVAS is recommended for patients with kidney damage. Glucocorticoid and antihypertensive agents are effective. Interventional therapy can be an option for patients with persistent hypertension.


The new Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry: design, rationale, and characteristics of patients enrolled in the first 12 months



Herein we describe the history, design, and rationale of the new Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry and present the characteristics of patients with juvenile idiopathic arthritis (JIA) enrolled in the first 12 months of operation.


The CARRA Registry began prospectively collecting data in the United States and Canada in July 2015 to evaluate the safety of therapeutic agents in persons with childhood-onset rheumatic disease, initially restricted to JIA. Secondary objectives include the evaluation of disease outcomes and their associations with medication use and other factors. Data are collected every 6 months and include clinical assessments, detailed medication use, patient-reported outcomes, and safety events. Follow-up is planned for at least 10 years for each participant and is facilitated by a telephone call center.


As of July 2016, 1192 patients with JIA were enrolled in the CARRA Registry at 49 clinical sites. At enrollment, their median age was 12.4 years old and median disease duration was 2.6 years. Owing to preferential enrollment, patients with systemic JIA (13%) and with a polyarticular course (75%) were over-represented compared to patients in typical clinical practice. Approximately 49% were currently using biologic agents and ever use of oral glucocorticoids was common (47%). The CARRA Registry provides safety surveillance data to pharmaceutical companies to satisfy their regulatory requirements, and several independently-funded sub-studies that use the Registry infrastructure are underway.


The new CARRA Registry successfully enrolled nearly 1200 participants with JIA in the first 12 months of its operation. Sustainable funding has been secured from multiple sources. The CARRA Registry may serve as a model for the study of other uncommon diseases.


Selective CDK4/6 Inhibitors in Cancer: Moving Beyond Breast Cancer

Learning Module - Richard Finn, MD; Gary K. Schwartz, MD; and Geoffrey Shapiro, MD, PhD, discuss the supporting rationale and emerging role of selective CDK4/6 inhibitors in multiple types of cancer.

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Flexible Piezoelectric-Induced Pressure Sensors for Static Measurements Based on Nanowires/Graphene Heterostructures

TOC Graphic

ACS Nano
DOI: 10.1021/acsnano.6b08027

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Biochemical alteration in children with idiopathic nephrotic syndrome associated with an increased risk of sensorineural hearing loss; additional insights in cochlear renal relationship

Children with Idiopathic Nephrotic Syndrome (INS) are at risk of hearing loss due to the adverse impact of medications and related immunological and genetic factors on both cochlea and kidney. So this work was planned to evaluate hearing status in children with INS and to clarify the possible associated risk factors by interpreting the clinical and laboratory profiles of those children.

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Comprehensive management of congenital choanal atresia

To present results of a one-stage minimally invasive surgical procedure for congenital choanal atresia (CCA). Seven outcome measures were applied.

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Left and right reaction time differences to the sound intensity in normal and AD/HD children

Right hemisphere, which is attributed to the sound intensity discrimination, has abnormality in people with attention deficit/hyperactivity disorder (AD/HD). However, it is not studied whether the defect in the right hemisphere has influenced on the intensity sensation of AD/HD subjects or not. In this study, the sensitivity of normal and AD/HD children to the sound intensity was investigated.

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Comparison of First Year of Life Acute Otitis Media Admissions Before and After the 13-Valent Pneumococcal Conjugate Vaccine

Acute otitis media (AOM) is a common childhood infection, which is usually managed in the outpatient setting. Yet, the more severe cases are referred for inpatient treatment. We hypothesized that pneumococcal conjugate vaccines (PCVs), administered during the first year of life, would decrease AOM admissions rate in this age group. We studied the characteristics of infants admitted with AOM and acute mastoiditis (AM) in the PCV13 era, routinely given from November 2010 to all infants.

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Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11

Existing literature only reports a few patients with Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) who underwent cochlear implantation (CI). The present study describes four NS patients and one NSML patient with a PTPN11 mutation. They all had severe to profound hearing loss, and they received a CI. The age at which the CI surgery occurred ranged from 1-13 years old, and the audiological results in all five patients improved after the CI. Otological and audiological examinations in NS and NSML are important, and for those with severe hearing loss, the CI surgery improved the audiological outcome regardless of age.

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Management of non-organic hearing loss in children – a case study

A 10 year-old girl was admitted due to the claim of progressively developing hearing loss. The impedance audiometry showed no abnormalities but it was impossible to obtain reliable outcomes during pure tone audiometry assessment. The girl was additionally sent for speech audiometry, indicating a bilateral hearing loss and objective evaluations such as distortion product otoacoustic emissions, and auditory brainstem responses, which results indicated a normal hearing. On the second day, repeated subjective audiometric tests showed also normal hearing, despite constantly reported hearing loss.

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The watch-pat in pediatrics sleep disordered breathing: Pilot study on children with negative nocturnal pulse oximetry

The main purpose of this study was to determine the efficacy of Watch-PAT in Pediatric Sleep Disordered Breathing (PSDB) diagnosis in children with symptoms suggestive of PSDB, in which the nocturnal pulse oximetry was negative according to the Brouilette criteria.

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Nasal ala reconstruction: Surgical conundrum


Ana Ortins-Pina, Ana Isabel Teixeira, Maria Sanches, Ana Isabel Gouveia, Paulo Leal Filipe, João Maia Silva

Journal of Cutaneous and Aesthetic Surgery 2017 10(1):55-58

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Should advertising by aesthetic surgeons be permitted?


Venkataram Mysore

Journal of Cutaneous and Aesthetic Surgery 2017 10(1):48-48

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Autologous platelet-rich fibrin matrix in non-healing trophic ulcers in patients with Hansen's disease


Umashankar Nagaraju, Priya K Sundar, Priyanka Agarwal, Belliappa P Raju, Mahesh Kumar

Journal of Cutaneous and Aesthetic Surgery 2017 10(1):3-7

Background: Non-healing trophic ulcers in Hansen's disease patients is one of the major causes for disability. It has been shown that autologous platelet-rich fibrin matrix (PRFM) is effective in healing chronic non-healing leg ulcers. Aim: The objective of this study is to demonstrate the efficacy of autologous platelet-rich fibrin matrix (PRFM) in non-healing trophic ulcers in patients treated for Hansen's disease. Design: A prospective study. Setting: An institution-based clinic. Participants: Seven treated patients with Hansen's disease, with a mean age of 38.33 years, with nine non-healing trophic ulcer of more than 6 weeks duration. Measurements: Photographs were taken before treatment and at every subsequent sitting. Area and volume were calculated at baseline and every subsequent sitting till the closure was achieved. Materials and Methods: The healthy ulcers were treated with PRFM at weekly intervals, repeated once a week for a maximum of five sittings as per requirement. Results: The mean percentage improvement in the area was 93.52%, and volume was 97.74% at the end of the second sitting. All ulcers closed by a maximum of five sittings. No adverse events were noted. Conclusion: PRFM for the treatment of trophic ulcers in treated patients with Hansen's disease is a feasible, safe, simple and inexpensive method.

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Accelerated wound healing: Harnessing the power of platelets, biomaterials, stem cells and gene therapy


Niti Khunger

Journal of Cutaneous and Aesthetic Surgery 2017 10(1):1-2

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Comparison of efficacy of autologous platelet-rich fibrin versus saline dressing in chronic venous leg ulcers: A randomised controlled trial


Anirudh Somani, Reena Rai

Journal of Cutaneous and Aesthetic Surgery 2017 10(1):8-12

Background: Venous leg ulcer is a chronic condition, and various treatment modalities are available. Platelet-rich fibrin (PRF) is one of the newer modalities and it contains fibroblast growth factor (GF), vascular endothelial GF, angiopoitin and platelet-derived GF which enhances the wound healing. Hence, we conducted a randomised controlled trial to compare the efficacy of PRF versus saline dressing in chronic venous leg ulcers. Aim: This study aims to compare the efficacy of autologous PRF with saline dressing in patients with chronic venous leg ulcer and to compare the mean reduction in ulcer area at the end of 4 weeks. Materials and Methods: Fifteen patients with chronic venous leg ulcers of >6 months duration having an ulcer area of 1 cm × 1 cm to 5 cm × 5 cm were taken into the study and were randomly divided into two groups. Group 1: Patients received PRF dressing. Ten millilitres of patient's blood was taken and centrifuged at 3000 rpm for 15 min. A fibrin clot obtained in the middle of the tube was removed and used for dressing over the wound surface. It was repeated every week for 4 weeks. Group 2: Patients received saline dressings once a week for 4 weeks. The assessment of the ulcer size was done with the help of photographs, and ulcer area was measured. Results: The mean reduction in the area of the ulcer size in PRF group was 85.51%, and the mean reduction in the area of the ulcer size in Saline group was 42.74% which was statistically significant with a P< 0.001 and t = 4.11. Conclusion: We conclude that PRF dressing can be used as it is effective, inexpensive, safe and an outpatient procedure.

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Plaque like giant dermatofibroma: A case report


Vinitha Varghese Panicker, Andezhuthu Divakaran Dharmaratnam, NV Seethalekshmy

Journal of Cutaneous and Aesthetic Surgery 2017 10(1):51-53

Dermatofibroma, also known as benign fibrous histiocytoma, is a soft-tissue tumour that usually occurs in the mid-adult life and shows a slight female predominance. Giant dermatofibroma, a very rare clinical variant, is characterised by its unusually large size, benign biological behaviour despite its large size and same histopathological characteristics as conventional dermatofibroma. We report a 63-year-old woman who presented with a large tumour on the scapular region which showed histopathological features of benign dermatofibroma.

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Using amniotic membrane as a novel method to reduce post-burn hypertrophic scar formation: A prospective follow-up study


Ali Akbar Mohammadi, Shima Eskandari, Hamed Ghoddusi Johari, Ata'ollah Rajabnejad

Journal of Cutaneous and Aesthetic Surgery 2017 10(1):13-17

Background: Several studies have shown that the application of amniotic membrane as a biological dressing in the management of burns is accompanied by rapid re-epithelialisation. In this follow-up study, we aimed to evaluate the possible role of amniotic membrane as an adjunct to split thickness skin grafting on reducing itching and severity of hypertrophic scar formation. Materials and Methods: From October 2013 to January 2015, in a prospective follow-up study, 54 patients (108 limbs) with second and third degree burns, covering 4%–15% of total body surface area (TBSA), were included in the study. All patients needed split-thickness skin grafts for burn-wound coverage. Selected patients had symmetric burns on two (upper or lower) extremities. Then, in every patient, the extremities were randomly divided into two groups: In one limb, the skin graft was traditionally fixed with skin staples (control group) and in the other limb, the skin graft was covered with an amniotic membrane (amnion group). Therefore, in every patient, the graft was covered with an amniotic membrane in one extremity and fixed with skin staples in the other extremity. Finally, after 6 months, the degree of itching and hypertrophic scar formation was compared between the two groups. Results: The study group was composed of 108 limbs in 54 patients (27 males and 27 females) with a mean age of 23.54 % 4.9 years and burn 9.03 % 2.69% TBSA. The patients were divided into two groups: 54 limbs in amnion group and 54 limbs in control group. In 59.25% of the cases, patient had less itching in the extremity covered with amniotic membrane. Furthermore, in 64.81% of the cases, patients had less hypertrophic scar formation in the extremity covered with amniotic membrane. These differences were statistically significant (P < 0.001). Conclusions: Amniotic membrane used as an adjunct in split thickness skin grafting is a novel modality which significantly reduces scar formation and itching that can be greatly distressing to burn patients. However, still more prospective well designed studies are needed to prove it.

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Successful management of dowling-degos disease with combination of Q-switched Nd: YAG and fractional carbon dioxide laser


Swagata Arvind Tambe, Priyanka Deelip Patil, Dattatray Gopal Saple

Journal of Cutaneous and Aesthetic Surgery 2017 10(1):60-62

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